This Ruth L Kirschstein National Research Service Award Postdoctoral Research Training Grant proposal is submitted in response to Program Announcement # PA-06-468 for applications to provide institutional T32 awards to train young researchers who will become independent investigators who will address important problems in human health. The application requests resources to support four physician/scientists each year with MD or MD/PhD degrees who will receive mentored research that focuses on the etiology, pathogenesis, and treatment of pediatric malignancies. The long-term goal of this program is to train new investigators who will improve the care of children with cancer. The rationale for the program is based on the well-documented need to provide mentored career development support for young scientists that will enable them to become fully independent and productive laboratory researchers. As such, they will be poised to improve the health of children with cancer throughout the world by bringing state-of-the-art expertise to bear on problems such as inherited predispostions, environmental factors, the toxic and relatively non-specific nature of current therapies, and long-term adverse effects of mutagenic treatments. The design of this program involves harnessing the expertise of world-class research scientists who will serve as mentors for interdisciplinary training. We believe UCSF has the vision, experience, and infrastructure to train the next generation of leaders in childhood cancer research. In this application, we provide evidence that the Department together with the broader UCSF research community comprise an exceptional environment for preparing young investigators for productive careers in this field and describe a comprehensive plan for training these individuals. This application is directly relevant to human health as it requests funds to support mentored career development for outstanding young physician/scientists who will become independent researchers in the field of childhood cancer. Programs like this one represent an investment in the future of public health as the researchers who are trained through this award will be equipped to harness state-of-the-art research techniques to attack a formidable health problem in the pediatric population. The long-term outcome of intensive and innovative training provided by this T32 award will be effective new treatments for childhood cancers.